Nucleic acids

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are linear macromolecules consisting of hundreds to millions of nucleotides. Two types of nucleic acids are found in all living cells. These macromolecules carry genetic information which according to the genetic code can be translated into proteins. Nucleic acids were discovered in 1869 by Friedrich Miescher who isolated these substances from human cells and later from the nuclei of cells of fishes and called them „nuclein“. Twenty years later, in 1889, R. Altman discovered the same substances in the nucleus of plant cells and suggested the name „nucleic acids“ for these polymers (macromolecules made up of many similar small molecules). The complex chemical composition of nucleic acids was first described in 1929 by P. Lavene. Nucleic acids consist of sugars, in particular the pentoses, ribose or 2-deoxy ribose, phosphate, the purine bases, adenine and guanine, and the pyrimidine bases cytosine, thymine and uracil. Consequently, the chemical structure connecting these components was elucidated and the term „nucleotide“ was coined for the repeating unit of the macromolecule, consisting of one sugar phosphate linked to one of the nucleobases. The bases were bound to the C-1’ carbon of the sugar by glycosidic bonds, and the phosphate group acts as a linker between adjacent nucleotides as an ester between the C-3’ and C-5’ of the sugars, respectively.

Subsequently, it was found that two structurally and functionally different types of nucleic acids exist, which differ also in their chemical composition. Deoxyribonucleic acid (DNA) is the nucleic acid with the largest molecular weight and contains 2-deoxyribose, phosphate, and the four bases, adenine (A), cytosine (C), guanine (G), and Thymine (T). Ribonucleic acid (RNA) contains ribose, phosphate, and the four bases, adenine (A), cytosine (C), guanine (G), and uracil (U). RNA is formed by the process of transcription in the nucleus of eukaryotic cells, which contain mainly four different forms of RNA:

  1. messenger RNA (mRNA), which is destined to be translated into protein with the help of ribosomes;
  2. ribosomal RNA (rRNA), which is a component of ribosomes with structural as well as catalytic function;
  3. transfer RNA (tRNA), which is the „adapter“ predicted by Francis Crick that serves to ensure that the correct amino acid which is bound to the tRNA is inserted into the growing polypeptide chain according to the genetic code; and
  4. a large and diverse group of so-called „small nuclear RNAs“ which among other functions serve to correctly splice those transcripts which contain introns thus producing mature mRNA.

Experimental proof that DNA is the genetic material was obtained first by Oswald Avery (1944) based on earlier observations by Frederick Griffiths (1928). In these experiments it was shown that DNA (and no other cellular component) could transfer infectivity to a non-virulent bacterial strain. However, this finding was only generally accepted by scientists around the world in 1952, after Hershey and Chase had shown that only DNA was transmitted from bacteriophage (bacterial viruses) to the next phage generation. The next problems to be solved were how genetic information is exactly duplicated during division of cells in an essentially error-free process called replication, and how the two copies of the genome are distributed to the two daughter cells resulting from cell division. A very low error frequency in these processes is necessary, because otherwise errors in gene sequences (that is, mutations) would occur too often, making life impossible.

In order to understand the mechanism of replication, it was necessary to determine the structure of DNA, which was achieved by X-ray diffraction experiments of DNA fibres (Rosalind Franklin, Maurice Wilkins) and model building (James Watson, Francis Crick) resulting in the well-known double helix (1953). Two linear DNA single strands are bound together by the so-called base pairs and are wound helically around a common axis. In the base pairs, binding is achieved by hydrogen bonds, joining every A with T, and every G with C. Hydrogen bonds are weak chemical bonds, which can be opened and closed as needed under physiological conditions in the cell. In order to actually open and close the double helix in the cell, a large number of additional proteins and enzymes are necessary, including helicases (unwinding enzymes). If a wrong nucleotide is incorporated (not according to the base pairing rules), a proof-reading mechanism is activated, and the wrong nucleotide is removed immediately after incorporation.

The structure of the double helix immediately indicates how DNA is replicated. The double helix is opened resulting in two single strands. Each single strand now functions as a template for the synthesis of a complementary strand according to the base pairing rules. Where the template contains the base A, the newly synthesized strand will contain T, and where the template contains G, the newly synthesized strand contains C. In this way, two identical double strands are produced. Subsequently in the cell division cycle, these two double strands (called chromatids in eukatyotic cells) are distributed to the two daughter cells by means of the mitotic spindle apparatus.

RNA is, except in some viruses, always single stranded. RNA represents transcripts of the DNA genome; only in some viruses is RNA itself the genome. All living cells contain the double-helical DNA as the genetic material.

The differences between all living organisms are based on their different DNA sequences. DNA sequences can be determined in the laboratory with high speed and accuracy and the sequences can be used to determine the relationship between two species or between two varieties of the same species. This has become very important for determination of the complicated relationship between different varieties of Vitis vinifera, the vine, and of course, the genetic identity of a variety of Vitis vinifera to a large degree determines the properties of the final product – wine. Of course, other factors besides the genetics of the plant are also immensely important, like the climate, the soil, and the microorganisms used for fermentation of the must. Sequence comparisons are not only possible between extant species, but also with fossil species, because DNA is so highly stable that it can be isolated and sequenced from fossilized biological material. This is extremely valuable for the determination of the nature of ancestral species in cases where the derivation of modern species is not entirely clear based on morphological criteria alone. In a remarkabe prediction in his book „What is life?“ the physicist Erwin Schrödinger has conjectured that DNA must be a chemically very stable molecule.

A functional unit of the DNA coding for one gene product (protein or RNA) is called a gene, the complex total DNA of a cell is called the genome. The genome of a human haploid cell or gamete contains about 22000 to 25000 genes. However, as we are diploid organisms, cells in the body contain twice that amount, as every gene exists in two copies, one inherited from the mother and the other from the father.

Our text dealing with nucleic acids is a simple minimum, like the following text about the laws of genetics. Further information can be gained from the literature in the fields of Molecular Biology and Molecular Genetics and it is recommended to use Wikipedia for an entrance into these fields.

Michael Breitenbach University of Salzburg Austria

Ian W. Dawes University of New South Wales Sydney Australia

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